The objectives of this proposal are to evaluate smoke exposure (SE) during fire overhauls and determine and characterize sensitive biomarkers of SE in firefighters (FF). Fire fighters frequently remove their self-contained breathing apparatus during overhauls (i.e., seeking and extinguishing hidden fire) despite potentially injurious SE. Preliminary work has demonstrated a decline in diffusing capacity to carbon monoxide (DLCO) associated with number of fires fought, while spirometry, usually the only test of lung function used in FF surveillance, remained stable. These provocative findings suggest possible chronic injury due to SE. The applicant proposes to validate these findings through evaluation of FF with biomarkers of lung injury potentially more sensitive to SE than spirometry, including serum (Clara cell protein, alveolar surfactant-associated proteins A and B), radiological (99mTc-DTPA lung clearance rate), and induced sputum (cell count, TNFalpha, 02) tests. The specific aims of the proposal are to: (1) characterize SE during overhaul; (2) use biomarkers to measure acute (<= 2hours) pulmonary effects in FF after overhaul; (3) explore the use of serum biomarkers as surveillance tools for chronic (>=1 year) pulmonary effects in FF; and (4) determine the ability of air purifying respirators to reduce pulmonary effects of SE during overhaul. The study design will use a cohort of 100 never-smoking Phoenix and Tucson FF who will be monitored for SE during overhaul of residential structural fires, and, in addition, will receive baseline and post-overhaul evaluation with the full set of biomarkers of lung injury. Phoenix intends to offer FF the use of air purifying respirators during overhaul. It is expected that the targeted biomarkers should provide sensitive measures of acute and chronic pulmonary injury in FF, and serve as well to evaluate the efficacy of workplace interventions designed to reduce SE.